tbuckley/cabot-search huggingface dataset:
Assessing the role of frailty status on surgical, oncologic and functional outcomes in patients treated with robot-assisted radical prostatectomy for prostate cancer
Authors: G. Rosiello, S. Scuderi, G. Gandaglia, E. Mazzone, F. Barletta, R. Leni, L. Toneatto, L. Quarta, D. Cannoletta, A. Pellegrino, G.M. Colandrea, D. Robesti, A. Stabile, F. Dehò, U. Capitanio, A. Larcher, A. Salonia, P.I. Karakiewicz, F. Montorsi, A. Briganti
Journal: European Urology (2022)
Prevalence and prognosis of BRCAm, homologous recombination repair mutation (HRRm) or HR deficiency positive (HRD+) across tumor types.
Authors: Changxia Shao, Yixin Ren, Heng Zhou, Cai Chen, Elisha Dettman, Razvan Cristescu, Alexander Gozman, Fan Jin, Wei Zhou
Journal: Journal of Clinical Oncology (2022)

e18802 Background: BRCAm, HRRm, or HRD+ may be predictive of response to poly (ADP-ribose) polymerase inhibitors (PARPi) with/without immunotherapy (IO). However, there is limited data on the prevalence of these biomarkers and their impact on overall survival (OS) among patients who are not treated with PARPi or IO. Methods: This is a retrospective observational study across 15 available tumor types, using data from the de-identified Flatiron Health - Foundation Medicine (FMI) clinicogenomic database collected up to Dec 31, 2020. The de-identified data originated from ̃280 US cancer clinics (̃800 sites of care). Eligible patients were aged ≥ 18 years, diagnosed with advanced/metastatic solid tumors in 2018-2019. BRCAm, HRRm, and HRD were assessed by FMI F1CDx. HRD+ was defined as genomic loss of heterozygosity (gLOH) ≥16. OS analysis from second line therapy initiation (2L, primary index date) was performed as primary analysis since this population had high unmet medical need, and most patients were sequenced after 1L. Patients were excluded if PARPi/IO started on the index date or earlier or if patients died before the index date; and patients were censored as of PARPi/IO initiation if PARPi/IO was started later than the index date. OS was analyzed using the Kaplan-Meier method and Cox proportional hazards model, adjusted for age, sex, and tumor type. Results: A total of 9,462 patients with advanced/metastatic solid tumors were included, with 52% women and mean age of 66 years. The top five tumor types represented more than 75% of the patients, including non-small cell lung cancer (27%), colorectal (19%), breast (13%), pancreatic (8%) and gastric (8%) cancers. Known or suspected deleterious BRCAm was observed in 4.6% of patients across tumors and varied by tumor type, with the highest prevalence in ovarian cancer (13.0%). Total HRRm prevalence was 13.2% across tumor types with prostate cancer (25.9%) as the highest, and the prevalence of HRD+ was 20.6% cross tumor types with breast cancer (34.4%) as the highest. The adjusted hazard ratio (aHR) for OS from initiation of 2L therapy for patients with BRCAm vs BRCA wild type (BRCAwt) was 0.81 (95%CI, 0.61-1.07). Comparable results were observed when calculating OS from 1L or 3L therapy. The aHR of OS from 2L therapy with HRRm vs HRRwt was 0.92 (0.78-1.09) and 1.20 (1.01-1.43) for patients with HRD+ vs HRD negative (HRD-). Conclusions: The prevalence of BRCAm, HRRm, and HRD+ varies widely by tumor type. There was no association between BRCA/HRRm status and OS, yet HRD+ might be associated with shorter OS among patients who were not treated with PARPi or IO across the evaluated tumor types.[Table: see text]
A phase II feasibility study of electronic patient reported outcomes (ePROs) for oral cancer directed therapies (OCDT).
Authors: Jim W Doolin, Ellana Haakenstad, Bridget A. Neville, Stuart R. Lipsitz, Sunyi Zhang, Jessica Cleveland, Semegne Hiruy, Michael J. Hassett, Anna C. Revette, Deborah Schrag, Ethan Basch, Nadine Jackson McCleary
Journal: Journal of Clinical Oncology (2022)

e13509 Background: Patients receiving oral cancer directed therapy (OCDT) may be at greater risk of toxicity and non-adherence than those on intravenous treatments. Electronic patient reported outcomes (ePROs) have the potential to mitigate those risks by alerting clinicians to patient status between visits, prompting earlier intervention. Best practices for ePROs implementation are not yet defined. We sought to demonstrate the feasibility of ePROs between visits for patients receiving OCDT both without and with asynchronous nursing triage calls for severe symptoms. Methods: In this Phase II feasibility study, patients were prospectively enrolled into two arms. In the first arm, “passive management” (Arm 1) patients were sent weekly ePROs with 15 symptoms, graded 0 (none) to 3 (severe), through the electronic patient portal (ePP). Responses were available for review by clinicians via the electronic medical record (EMR). In the second arm, “active management” (Arm 2) patients received the same weekly ePROs. If a patient responded with a severe symptom, a nurse would call within one business day to triage the concern. The primary outcome was 30-day feasibility, defined as a patient responding to 50% or more of ePROs sent during this period. Secondary outcomes included feasibility at 60- and 90-days, unplanned healthcare utilization (urgent care, ED visit or hospitalization), and nursing calls. At the time the Arm 2 was enrolling, a language-concordant interface for the EMR and ePP became available. The study was amended to include primarily Spanish speaking patients with a language concordant ePROs survey. Results: 100 patients were enrolled, 50 per arm. 10 patients who primarily spoke Spanish were included in Arm 2; the remaining 90 patients were fluent in English. 96 patients were eligible for evaluation of 30-day feasibility, 92 for 60-day, and 86 for 90-day. The 30-day feasibility by arm was 57% in Arm 1 and 45% in Arm 2 (p = 0.26). The 30-day feasibility in the Spanish language subgroup of the Arm 2 was 56%. Nursing calls in the first 30-days were 101 in Arm 1 and 109 in Arm 2. Multivariable regression for predictors of responding to 50% or more of ePROs in days 0-30 did not identify statistically significant correlates of feasibility. Conclusions: ePROs administered via an ePP were feasible the first 30 days on oral cancer directed treatment. Adding nurse triage calls between visits and a language concordant process for primarily Spanish speaking patients were feasible. Larger studies are needed to determine which factors truly impact use of the program and, most importantly, adherence and quality of life.[Table: see text]
National and local racial disparities in triple-negative breast cancer (TNBC) survival: Local outcomes counter the myth of national averages.
Authors: Ibrahim M. Abbass, Joshua A. Roth, Kimberly Jinnett, Veronica Zimmerman, Lourenia Cassoli
Journal: Journal of Clinical Oncology (2022)

e18588 Background: Real-world studies comparing racial differences in overall survival (OS) outcomes between African American (AA) and White (W) patients (pts) with TNBC have yielded mixed findings. This exploratory study assessed differences between national and county-level OS estimates-comparing AA vs. W pts, and identifying counties with greater racial disparities for future research. Methods: This retrospective cohort study used the Surveillance Epidemiology and End Result (SEER) cancer registry to assess county-level OS among non-hispanic AA and W pts ≥18 years of age who were diagnosed with TNBC 2011-2016. Counties with low levels of racial diversity (&lt; 30 AA or W TNBC pts) were excluded. Five-year OS was evaluated using Kaplan-Meier and multilevel parametric OS models with a Weibull distribution. By county, OS differences between AA and W pts were tested using linear hypothesis tests after model estimation. OS models were adjusted for age at diagnosis, year of diagnosis, marital status, insurance type, surgery type, stage, grade and metastasis at brain, bone, liver and lung. Results: Among 46,125 TNBC pts in SEER, 15,723 pts (33.4% AA, 66.6% W) residing in 8 States and 47 Counties met inclusion criteria. W pts were older (mean 60; ∓14 vs 57∓13 for AA) and more likely to be married (57% vs 33%), insured (49% vs 45%) and diagnosed at an earlier stage (stage I 37% vs 29%). Controlling for potential confounders, AA pts were more likely to experience 5-year mortality compared to W pts (Hazard Ratio [HR] = 1.16; 95%CI = 1.07, 1.26). Among 47 included counties, only 4 counties demonstrated a statistically significant 5-year OS racial disparities after adjusting for confounders. The difference in HRs between AA and W pts in these 4 counties ranged from 1.49 to 2.26 as depicted in the result table (p value &lt; 0.05). Removing these 4 counties (n = 2,929) from the final analytic cohort yielded statistically non-significant estimates (HR = 1.06; 0.97,1.16). Conclusions: There is clinically meaningful OS variation between AA and W pts with TNBC across U.S. counties included in SEER. Measuring disparities at the national or state level may mask important OS disparities at the county level. Using a county-level analytic approach, we were able to identify localities that disproportionately contribute to OS disparities at the national level. Our findings will facilitate better targeting of local interventions to address TNBC racial disparities. Future analyses should also assess counties excluded (n = 13,032) for small population sizes and/or low levels of racial diversity, as well as states not represented in SEER.[Table: see text]
LGG-39. Ascites in a medullary and leptomeningeal ganglioglioma patient following cisplatin treatment necessitating cessation of therapy and conversion to VA shunt
Authors: Evan Cantor, Andrea Ogle, Ashley Meyer, Margaret Shatara, Nicole M Brossier, Mohamed S Abdelbaki, Jennifer Strahle, Andrew Cluster
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Ganglioglioma is a low grade neoplasm consisting of dysplastic neuronal and neoplastic glial cells and accounts for 5% of pediatric CNS tumors. Management often includes CNS diversion. There have been case reports in which platinum containing chemotherapy has been thought to contribute to CSF malabsorption leading to ascites. CASE: A 13 month old male developed progressive macrocephaly, developmental delay, chronic emesis, and intermittent bilateral cranial nerve VI palsy over the 5 months prior to presentation. MRI brain/spine was significant for an enhancing nodule in the left posterior lateral medulla, nodular thickening and enhancement along the brainstem down to the conus medullaris and in the tentorium, with associated hydrocephalus. Biopsy of the medullary nodule and of the enhancement were consistent with ganglioglioma with BRAF-KIAA1549 fusion, equivocal MYCN amplification, and no BRAF V600E mutation. A ventriculo-peritoneal shunt was placed at the time of biopsy. Therapy was initiated with vincristine (1.5 mg/m2) and carboplatin (175 mg/m2.) Following the 12 week induction phase of therapy, he developed increasing diarrhea, emesis, and abdominal ascites. Peritoneal fluid analysis had no malignant cells and low protein compared to CSF. Ascites was responsive to drainage but would rapidly re-accumulate. Ultimately the patient’s chemotherapy was discontinued after 2 maintenance cycles due to continued symptoms. Acetazolamide was trialed but discontinued due to side effects, so its efficacy could not be determined. He underwent shunt externalization followed by venticulo-atrial (VA) shunt re-internalization. He has not had ascites since that time, at 4 months from surgery. His CNS disease burden has been stable at 6 months off therapy. DISCUSSION: Ascites was most likely due to CSF malabsorption in the abdomen with a possible contribution from platinum containing chemotherapy and less likely secondary to malignant peritoneal cells. Resolution since VA shunt internalization makes alternate explanations less likely.
The effect of azithromycin on structural lung disease in infants with cystic fibrosis (COMBAT CF): a phase 3, randomised, double-blind, placebo-controlled clinical trial
Authors: Stephen M Stick, Alexia Foti, Robert S Ware, Harm A W M Tiddens, Barry S Clements, David S Armstrong, Hiran Selvadurai, Andrew Tai, Peter J Cooper, Catherine A Byrnes, Yvonne Belessis, Claire Wainwright, Adam Jaffe, Philip Robinson, Lisa Saiman, Peter D Sly
Journal: The Lancet Respiratory Medicine (2022)
MEDB-33. The landscape of ecDNA in medulloblastoma
Authors: Owen Chapman, Sunita Sridhar, Shanqing Wang, Jon Larson, Robert Wechsler-Reya, Jill Mesirov, Lukas Chavez
Journal: Neuro-Oncology (2022)

Abstract Extrachromosomal circular DNA (ecDNA) is an important driver of aggressive cancers, including medulloblastoma (MB), the most common malignant pediatric brain tumor. To assess the clinical importance of ecDNA in MB, we applied computational methods to detect ecDNA in the genomes of a cohort of 468 MB patients and 31 MB model systems. Among patients, ecDNA was detected in 18% of tumors and carried a threefold greater risk of mortality. Affected genomic loci harbor up to hundredfold amplification of oncogenes including MYC, MYCN, TERT, and other novel putative oncogenes. Between sequential patient biopsies at initial diagnosis and subsequent relapse, we observed structural variation at ecDNA loci and generation of new ecDNA sequences. Among model systems, ecDNA was found in 19 of 31 genomes (61%). Although ecDNA was far more prevalent among MB models than patients, the ecDNA genomic sequences were conserved between most patient-derived xenograft (PDX) models and the human tumors from which they were made. To elucidate the functional regulatory landscapes of ecDNAs in MB, we generated transcriptional (RNA-seq), accessible chromatin (ATAC-seq), and chromatin interaction (Hi-C) profiles of 6 MB tumor samples. In each case, we identified regulatory interactions that cross fusion breakpoints on the ecDNA, representing potential “enhancer rewiring” events which may contribute to transcriptional activation of co-amplified oncogenes. To test this hypothesis, we are currently conducting in vitro CRISPRi screens targeting regulatory regions on the ecDNA of a MB cell line to determine whether these enhancers promote proliferation. Using single-cell sequencing, we have also begun exploring intratumoral heterogeneity of ecDNA in a p53-mutant SHH MB patient tumor and its corresponding PDX model. In summary, our study analyzes the frequency, diversity, and functional relevance of ecDNA across MB subgroups and provides strong justification for continued mechanistic studies of ecDNA in MB with the potential to uncover new therapeutic approaches.
Mode of detection of second breast cancers in patients undergoing surveillance after treatment of ductal carcinoma in situ.
Authors: Bethany Waites, Liisa Lyon, Gillian Kuehner, Patience Odele, Laurel A. Habel, Aida Shirazi, Raymond Liu
Journal: Journal of Clinical Oncology (2022)

571 Background: The incidence of ductal carcinoma in situ (DCIS) has increased, resulting in more women undergoing post-treatment surveillance for second breast cancers. National Comprehensive Cancer Network (NCCN) guidelines recommend annual breast imaging and physical exam every 6-12 months for five years, and then annually. We assessed mode of detection (imaging, patient-reported, or physical exam) of secondary DCIS and/or invasive breast cancer in a large cohort of DCIS patients undergoing surveillance after treatment of primary DCIS. Methods: We performed a retrospective cohort study of DCIS patients treated between 1/1/2008 and 1/1/2011 within a large integrated health care system. Patients had a minimum of 5 years of follow up. Patient demographics, treatment for primary DCIS, and tumor characteristics (of both primary DCIS and secondary cancer) were obtained from the electronic health record or from manual chart review. Chart review also included mode of detection of secondary breast cancers. Results: Our study cohort consisted of 1561 women with DCIS, with a median age of 59 years (range 32-92) at time of diagnosis. Among initial DCIS tumors, tumor grade was low/intermediate in 942 (60.3%) and high in 619 (39.7%); 1274 (81.6%) were estrogen receptor positive, and 988 (63.3%) progesterone receptor positive. Surgical treatment for the initial DCIS included lumpectomy (n=1134, 72.6%), unilateral mastectomy (n=320, 20.5%), or bilateral mastectomy (n=61, 3.9%), and included sentinel lymph node biopsy in 211 (14%) of patients. Additionally, 691 (44.3%) received radiation therapy and 440 (28.2%) received endocrine therapy. The cohort was followed for a median of 120 months, during which we identified 179 women (11.5%) with a secondary cancer detected at a median time of 57 months. Of the second breast cancers, 77 (43.0%) were ipsilateral, 98 (54.8%) contralateral, and 4 (2.2%) presented with distant metastases; 110 (61.5%) were invasive, 65 (36.3%) were DCIS, and 4 (2.2%) Paget’s disease. See table for mode of detection of second breast cancers. Conclusions: In our cohort of patients undergoing surveillance following initial diagnosis and treatment of DCIS, 2% of secondary breast cancers were detected by clinical breast exam, a rate similar to incidental detection at time of plastic surgery. These results can help inform future recommendations for surveillance of second breast cancers in DCIS patients. [Table: see text]
MEDB-02. The identification and functional characterization of circular RNA Circ_63706 in sonic hedgehog medulloblastomas
Authors: Rudramani Pokhrel, Keisuke Katsushima, Stacie Stapleton, George Jallo, Eric Raabe, Charles G Eberhart, Ranjan J Perera
Journal: Neuro-Oncology (2022)

Abstract Circular RNAs (circRNAs) are increasingly recognized as stable and specific biomarkers and therapeutic targets in many cancers, but little is known about their function, subtype specificity, and biomarker potential in medulloblastomas. Medulloblastoma is a central nervous system tumor that predominantly affects children and always requires aggressive therapy. Understanding and identifying novel disease-related molecular mechanisms and pathways are essential for developing optimal and novel therapies. To identify medulloblastoma subgroup-specific circRNAs, we subjected RNA-seq data from 175 clinical medulloblastoma samples representing the four subgroups to a statistical and machine learning (random forest classification) pipeline. Circular RNA circ_63706 expression was specific to the sonic hedgehog (SSH) group, which was confirmed through in situ hybridization analysis of clinical tissue samples. Functional characterization of circ_63706 by siRNAs and shRNAs demonstrated that cell proliferation, invasion, and apoptosis are perturbed in circ_63706 cells and inhibited in vivo tumor growth. These novel medulloblastoma-specific circular RNAs are emerging as important oncogenes that not only provide valuable mechanistic insights into how medulloblastomas develop but also how they can be used as biomarkers and therapeutic targets. These results pave the way for the specific identification and personalized treatment of different medulloblastoma subgroups.
Body composition parameter as risk predictor in metastatic renal cell carcinoma (mRCC)?
Authors: Constantin Heetfeld, Bennet Hensen, Hendik Eggers, Inga Peters, Markus A Kuczyk, Viktor Grünwald, Philipp Ivanyi
Journal: Journal of Clinical Oncology (2022)

e16506 Background: Imaging-derived data for patient’s (pts) prognostication in advanced/metastatic (m)RCC remains scarce. Recently, imaging body composition parameters such as muscle radiation attenuation (MA) and skeletal muscle index (SMI) as prognostic markers for cancer became a matter of interest. Here, impact of MA and SMI in mRCC pts, treated in our tertiary center, were retrospectively investigated. Methods: During the observation period 01/03 – 05/16, 401 pts mRCC receiving first line medical treatment were identified and analyzed. Pts were included for MA- and SMI-analysis based on Computed tomography (CT) scan data and recorded height and bodyweight, respectively. SMI and MA were assessed by a self-designed software-module using MeVisLab. SMI- and MA-subgroups were established by cutoff points, established using an optimum risk stratification method. Descriptive statistics and overall survival (OS) with Log-rank analysis were administered. Parameters with differences in MA-subgroups (p &lt; 0.2) were analyzed with univariable and multivariable Cox-Regression, once p &lt; 0.2 at each subsequent step. Results: 133 pts were eligible for MA-, 123 pts for SMI-analysis. The median age was 62 (range: 39-84) years, and 65.4% of pts showed an ECOG = 0. 87/133 (65.4%) and 71/123 (57.7%) pts showed low MA and low SMI, respectively. At time of mRCC diagnosis pts with low MA were significantly older (mean: 65 vs. 58 years, p &lt; 0,001), while T-, N-, and M-status, as well as MSKCC did not differ. Low MA was associated with a median OS of 27 (95% CI: 17,1-36.3) mo., compared to 60 (95% CI: 36.7-83.3) mo. for high MA (Log-Rank p = 0.001). Multivariable analysis identified low MA as an independent risk factor for OS (HR 2.07; 95% CI 1.24-3.48; p = 0.006). SMI did not reach significance (p = 0.1) (Tab.1). Conclusions: Here, MA provided a robust prognostic parameter regarding OS in mRCC pts. Interestingly, SMI showed no prognostic impact. CT-derived MA could be a promising addition to existing risk-scores. Further research is needed to validate these finding.[Table: see text]
Gender and weight change, skeletal muscle index(SMI) change, and survival in advanced non-small cell lung cancer(NSCLC) patients(pts.) receiving platinum chemotherapy.
Authors: Mary Jo J. Fidler, Palmi Shah, Hita Moudgalya, Marta Batus, Jeffrey Allen Borgia, Philip D. Bonomi
Journal: Journal of Clinical Oncology (2022)

e24080 Background: Significantly longer OS has been reported in advanced NSCLC pts. who gained weight or maintained (skeletal muscle mass) SMI during treatment with platinum containing chemotherapy. None of these studies evaluated the relationship between OS and both weight and SMI. Sex specific distributions are described for cachexia and muscle wasting. Methods: The objective of this retrospective study was to evaluate the relationships between OS and both weight gain and SMI maintenance during front line chemotherapy in advanced NSCLC pts. Weight and SMI measurements(cm 2 /m 2 ) were done at baseline and at 6, 12, &amp; 24 weeks. OS was estimated using the Kaplan-Meier method. The associations of weight and SMI with overall survival were assessed using Kaplan-Meier, log-rank test and proportional hazards regression. Results with p &lt; 0.05 were reported as significant. Results: Characteristics for the 88 patients were: median age – 64 years, women – 57%, caucasian – 68%, black – 25%, and adenocarcinoma histology – 63%. Weight gain (i.e., &gt; 0%) and &gt; 5% weight gain were observed in 50% and 11.3% of the patients, respectively. For all 88 patients the hazard ratio(HR) for OS in patients with &gt; 0% vs &lt; 0% weight change was 0.544 (p = 0.0164), and the HR for OS for weight &gt; 5% vs &lt; 5% was 0.469 (p = 0.099). The HR for OS in men for &gt; 0% vs &lt; 0% weight gain was 0.421(p = 0.031), and HR for OS &gt; 5% vs &lt; 5% weight gain was 0.421 (p = 0.031). The same analyses in women showed no significant differences. Increases in SMI &gt; 0% and &gt; 5% SMI were found in 48% and 35% of patients, respectively. Maintenance of SMI defined as &gt; - 1.3% was observed in 25% of pts. The HR for OS in men with SMI maintenance versus loss was 0.230 (p = 0.031), and the HR for OS in men with SMI increase &gt; 5% vs &lt; 5% was 0.219 (p = 0.0267). Neither SMI gain nor maintenance were significantly related to OS in the entire patient group or in women. Conclusions: In patients treated with first line platinum doublet, as a group there were no significant relationships between weight changes or SMI changes and OS. The observation that either weight gain or SMI maintenance was associated with longer OS in men only is based on data from a small number of patients. However, if larger studies show similar results, these findings could have implications for clinical and translational research in cachexia.